Por favor, use este identificador para citar o enlazar a este item:
http://hdl.handle.net/10261/66116
COMPARTIR / EXPORTAR:
SHARE CORE BASE | |
Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE | |
Título: | 2-Deoxy-d-glucose cooperates with arsenic trioxide to induce apoptosis in leukemia cells: Involvement of IGF-1R-regulated Akt/mTOR, MEK/ERK and LKB-1/AMPK signaling pathways |
Autor: | Estañ, María Cristina CSIC; Calviño, Eva CSIC ORCID ; Blas, Elena de CSIC; Boyano-Adánez, María del Carmen; Mena, María Luz; Gómez-Gómez, Milagros; Rial, Eduardo CSIC ORCID ; Aller, Patricio CSIC | Palabras clave: | 2-Deoxy-d-glucose Arsenic trioxide Apoptosis protein kinases Leukemia cells |
Fecha de publicación: | 15-dic-2012 | Editor: | Elsevier | Citación: | Biochemical Pharmacology 84(12):1604-1616(2012) | Resumen: | While the anti-tumor efficacy of 2-deoxy-d-glucose (2-DG) is normally low in monotherapy, it may represent a valuable radio- and chemo-sensitizing agent. We here demonstrate that 2–10 mM 2-DG cooperates with arsenic trioxide (ATO) and other antitumor drugs to induce apoptosis in human myeloid leukemia cell lines. Using ATO and HL60 as drug and cell models, respectively, we observed that 2-DG/ATO combination activates the mitochondrial apoptotic pathway, as indicated by Bid-, and Bax-regulated cytochrome c and Omi/HtrA2 release, XIAP down-regulation, and caspase-9/-3 pathway activation. 2-DG neither causes oxidative stress nor increases ATO uptake, but causes inner mitochondria membrane permeabilization as well as moderate ATP depletion, which nevertheless do not satisfactorily explain the pro-apoptotic response. Surprisingly 2-DG causes cell line-specific decrease in LKB-1/AMPK phosphorylation/activation, and also causes Akt/mTOR/p70S6K and MEK/ERK activation, which is prevented by co-treatment with ATO. The use of kinase-specific pharmacologic inhibitors and/or siRNAs reveals that apoptosis is facilitated by AMPK inactivation and restrained by Akt and ERK activation, and that Akt and ERK activation mediates AMPK inhibition. Finally, 2-DG stimulates IGF-1R phosphorylation/activation, and co-treatment with IGF-1R inhibitor prevents 2-DG effects on Akt, ERK and AMPK, and facilitates 2-DG-provoked apoptosis. In summary 2-DG elicits IGF-1R-mediated AMPK inactivation and Akt and ERK activation, which facilitates or restrain apoptosis, respectively. 2-DG-provoked AMPK inactivation increases the apoptotic efficacy of ATO, while in turn ATO-provoked Akt and ERK inactivation may increase the efficacy of 2-DG as anti-tumor drug | Descripción: | 9 páginas, 9 figuras, 2 figuras suplementarias -- PAGS nros. 1604-1616 | Versión del editor: | http://dx.doi.org/10.1016/j.bcp.2012.09.022 | URI: | http://hdl.handle.net/10261/66116 | DOI: | 10.1016/j.bcp.2012.09.022 | ISSN: | 0006-2952 | E-ISSN: | 1873-2968 |
Aparece en las colecciones: | (CIB) Artículos |
Ficheros en este ítem:
Fichero | Descripción | Tamaño | Formato | |
---|---|---|---|---|
restringido.pdf | 21,67 kB | Adobe PDF | Visualizar/Abrir |
CORE Recommender
SCOPUSTM
Citations
38
checked on 31-mar-2024
WEB OF SCIENCETM
Citations
37
checked on 22-feb-2024
Page view(s)
340
checked on 23-abr-2024
Download(s)
265
checked on 23-abr-2024
Google ScholarTM
Check
Altmetric
Altmetric
NOTA: Los ítems de Digital.CSIC están protegidos por copyright, con todos los derechos reservados, a menos que se indique lo contrario.